Differential expression of TGF-β, IL-2, and other cytokines in the CNS of Theiler's murine encephalomyelitis virus-infected susceptible and resistant strains of mice
Differential expression of TGF-β, IL-2, and other cytokines in the CNS of Theiler's murine encephalomyelitis virus-infected susceptible and resistant strains of mice
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DOI：
10.1006/viro.2000.0646
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发表时间：
2000-12-20
期刊：
影响因子：
3.7
通讯作者：
Oleszak, EL
中科院分区：
文献类型：
--
作者：
Chang, JR;Zaczynska, E;Oleszak, EL
易感的SJL小鼠颅内接种泰勒氏小鼠脑脊髓炎病毒(TMEV)可导致双相疾病，包括早期急性疾病，随后是与单核细胞浸润和脱髓鞘病变相关的晚期慢性脱髓鞘疾病。相比之下，耐药的C57BL/6(B6)小鼠只出现早期急性疾病。我们用细胞因子特异性RT-PCR方法检测了TMEV感染的SJL和B6小鼠中枢神经系统细胞因子转录产物的表达。在早期急性疾病中，我们在感染TMEV的SJL和B6小鼠的中枢神经系统中都发现了强烈的促炎细胞因子反应，表现为干扰素-γ、IL-L、IL-6、IL-12p40和肿瘤坏死因子-α的转录表达。在感染后第8天，SJL易感小鼠中枢神经系统中转化生长因子-β1和肿瘤坏死因子-α的转录水平显著高于B6小鼠(P<；0.01)。免疫组织化学染色显示，SJL组小鼠脑内软脑膜单个核炎性细胞浸润物中有转化生长因子-1蛋白表达，而B6组小鼠脑内未见表达。转化生长因子-β可能是SJL小鼠未能产生有效的抗TMEV CTL反应的原因。在慢性脱髓鞘疾病晚期，SJL小鼠中枢神经系统中发现高水平的促炎性Th1细胞因子，而B6小鼠则未见。TMEV感染的SJL慢性脱髓鞘小鼠脊髓中抗炎细胞因子IL-4、IL-5、IL-10(Th2细胞因子)和转化生长因子-α的表达水平显著高于同期(P<；0.01)的B6小鼠。这些抗炎细胞因子可能参与了SJL小鼠促炎反应的下调。感染TMEV的SJL小鼠在脱髓鞘疾病发作之前，脊髓中出现高水平的IL-2转录本和蛋白，并与新的T细胞进入中枢神经系统和/或病毒清除后未被消除的剩余T细胞的扩张相一致。(C)2000年学术出版社。
Intracranial inoculation of susceptible SJL mice with Theiler's murine encephalomyelitis virus (TMEV) results in biphasic disease consisting of early acute disease, followed by late chronic demyelinating disease, associated with mononuclear infiltrates and demyelinating lesions. In contrast, resistant C57BL/6 (B6) mice develop only early acute disease. We employed cytokine-specific RT-PCR to determine the expression of cytokine transcripts in the CNS of TMEV-infected SJL and B6 mice. During early acute disease, we have found a strong proinflammatory (Th1) cytokine response in the CNS of both TMEV-infected SJL and B6 mice, demonstrated by the expression of transcripts for IFN-gamma, IL-l, IL-6, IL-12p40, and TNF-alpha. At 8 days postinfection (p.i.), TGF-beta1 and TNF-alpha transcripts were present at significantly higher levels (P < 0.01) in the CNS of SJL susceptible mice in comparison to those found in the CNS of B6 mice. Immunohistochemical staining revealed that TGF- protein was expressed in leptomeningeal mononuclear inflammatory cell infiltrates in the brain of SJL mice but not in B6 mice, at 8 days p.i. TGF-beta may be responsible for the failure of SJL mice to develop an effective anti-TMEV CTL response. During late chronic demyelinating disease, high levels of proinflammatory Th1 cytokines were found in the CNS of SJL mice, but not B6 mice. Significantly higher levels (P < 0.01) of anti-inflammatory cytokine transcripts (IL-4, IL-5, and IL-10 (Th2 cytokines) and TGF-) were found in the spinal cord of TMEV-infected SJL mice with chronic demyelinating disease than in the spinal cord of B6 mice during the same time period (39 or 60 days p.i.). These anti-inflammatory cytokines may contribute to the downregulation of the proinflammatory response in SJL mice. High levels of IL-2 transcripts and protein appeared transiently in the spinal cord of TMEV-infected SJL mice before the onset of demyelinating disease and coincided with an influx of new T cells into the CNS and/or expansion of remaining T cells that have not been eliminated after viral clearance. (C) 2000 Academic Press.